Predicting Shine–Dalgarno Sequence Locations Exposes Genome Annotation Errors

In prokaryotes, Shine–Dalgarno (SD) sequences, nucleotides upstream from start codons on messenger RNAs (mRNAs) that are complementary to ribosomal RNA (rRNA), facilitate the initiation of protein synthesis. The location of SD sequences relative to start codons and the stability of the hybridization between the mRNA and the rRNA correlate with the rate of synthesis. Thus, accurate characterization of SD sequences enhances our understanding of how an organism's transcriptome relates to its cellular proteome. We implemented the Individual Nearest Neighbor Hydrogen Bond model for oligo–oligo hybridization and created a new metric, relative spacing (RS), to identify both the location and the hybridization potential of SD sequences by simulating the binding between mRNAs and single-stranded 16S rRNA 3′ tails. In 18 prokaryote genomes, we identified 2,420 genes out of 58,550 where the strongest binding in the translation initiation region included the start codon, deviating from the expected location for the SD sequence of five to ten bases upstream. We designated these as RS+1 genes. Additional analysis uncovered an unusual bias of the start codon in that the majority of the RS+1 genes used GUG, not AUG. Furthermore, of the 624 RS+1 genes whose SD sequence was associated with a free energy release of less than −8.4 kcal/mol (strong RS+1 genes), 384 were within 12 nucleotides upstream of in-frame initiation codons. The most likely explanation for the unexpected location of the SD sequence for these 384 genes is mis-annotation of the start codon. In this way, the new RS metric provides an improved method for gene sequence annotation. The remaining strong RS+1 genes appear to have their SD sequences in an unexpected location that includes the start codon. Thus, our RS metric provides a new way to explore the role of rRNA–mRNA nucleotide hybridization in translation initiation

An experimental evaluation of software redundancy as a strategy for improving reliability

The strategy of using multiple versions of independently developed software as a means to tolerate residual software design faults is suggested by the success of hardware redundancy for tolerating hardware failures. Although, as generally accepted, the independence of hardware failures resulting from physical wearout can lead to substantial increases in reliability for redundant hardware structures, a similar conclusion is not immediate for software. The degree to which design faults are manifested as independent failures determines the effectiveness of redundancy as a method for improving software reliability. Interest in multi-version software centers on whether it provides an adequate measure of increased reliability to warrant its use in critical applications. The effectiveness of multi-version software is studied by comparing estimates of the failure probabilities of these systems with the failure probabilities of single versions. The estimates are obtained under a model of dependent failures and compared with estimates obtained when failures are assumed to be independent. The experimental results are based on twenty versions of an aerospace application developed and certified by sixty programmers from four universities. Descriptions of the application, development and certification processes, and operational evaluation are given together with an analysis of the twenty versions

Toward a first-principles integrated simulation of tokamak edge plasmas

Performance of the ITER is anticipated to be highly sensitive to the edge plasma condition. The edge pedestal in ITER needs to be predicted from an integrated simulation of the necessary first-principles, multi-scale physics codes. The mission of the SciDAC Fusion Simulation Project (FSP) Prototype Center for Plasma Edge Simulation (CPES) is to deliver such a code integration framework by (1) building new kinetic codes XGC0 and XGC1, which can simulate the edge pedestal buildup; (2) using and improving the existing MHD codes ELITE, M3D-OMP, M3D-MPP and NIMROD, for study of large-scale edge instabilities called Edge Localized Modes (ELMs); and (3) integrating the codes into a framework using cutting-edge computer science technology. Collaborative effort among physics, computer science, and applied mathematics within CPES has created the first working version of the End-to-end Framework for Fusion Integrated Simulation (EFFIS), which can be used to study the pedestal-ELM cycles

PKD1 and PKD2 mutations in Slovenian families with autosomal dominant polycystic kidney disease

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder caused by mutations in at least two different loci. Prior to performing mutation screening, if DNA samples of sufficient number of family members are available, it is worthwhile to assign the gene involved in disease progression by the genetic linkage analysis. METHODS: We collected samples from 36 Slovene ADPKD families and performed linkage analysis in 16 of them. Linkage was assessed by the use of microsatellite polymorphic markers, four in the case of PKD1 (KG8, AC2.5, CW3 and CW2) and five for PKD2 (D4S1534, D4S2929, D4S1542, D4S1563 and D4S423). Partial PKD1 mutation screening was undertaken by analysing exons 23 and 31–46 and PKD2 . RESULTS: Lod scores indicated linkage to PKD1 in six families and to PKD2 in two families. One family was linked to none and in seven families linkage to both genes was possible. Partial PKD1 mutation screening was performed in 33 patients (including 20 patients from the families where linkage analysis could not be performed). We analysed PKD2 in 2 patients where lod scores indicated linkage to PKD2 and in 7 families where linkage to both genes was possible. We detected six mutations and eight polymorphisms in PKD1 and one mutation and three polymorphisms in PKD2. CONCLUSION: In our study group of ADPKD patients we detected seven mutations: three frameshift, one missense, two nonsense and one putative splicing mutation. Three have been described previously and 4 are novel. Three newly described framesfift mutations in PKD1 seem to be associated with more severe clinical course of ADPKD. Previously described nonsense mutation in PKD2 seems to be associated with cysts in liver and milder clinical course

Armadillo 1.1: An Original Workflow Platform for Designing and Conducting Phylogenetic Analysis and Simulations

In this paper we introduce Armadillo v1.1, a novel workflow platform dedicated to designing and conducting phylogenetic studies, including comprehensive simulations. A number of important phylogenetic and general bioinformatics tools have been included in the first software release. As Armadillo is an open-source project, it allows scientists to develop their own modules as well as to integrate existing computer applications. Using our workflow platform, different complex phylogenetic tasks can be modeled and presented in a single workflow without any prior knowledge of programming techniques. The first version of Armadillo was successfully used by professors of bioinformatics at Université du Quebec à Montreal during graduate computational biology courses taught in 2010–11. The program and its source code are freely available at: <http://www.bioinfo.uqam.ca/armadillo>

Use of MID-MIX® treated sewage sludge in cement mortars and concrete

Developing beneficial applications for sewage sludge is a key challenge in many countries, given the amount of sludge generated and the disposal or recycling options currently available. Sewage sludge from the wastewater treatment plant at Koprivnica in Croatia has been treated using MID-MIX ® technology that involves the addition of Ca(OH) 2 and CaO to dewatered sludge. This produces a low-density non-hazardous white-grey powder. The treated sewage sludge has been heated to 800, 900 and 1000 °C to form MID-MIX ® treated sewage sludge ash with reduced organic content. MID-MIX ® treated sewage sludge and ash have been used to replace 10 and 20% of cement in mortar and concrete samples. The addition of MID-MIX ® treated sewage sludge causes a significant increase in void content which reduces the mechanical properties and durability of mortar and concrete samples. However, replacement of cement by MID-MIX ® ash did not significantly affect the strength, water penetration or gas permeability compared to control samples. Leaching tests on MID-MIX ® powder, MID-MIX ® ash and mortar samples produced low levels of heavy metal release. The research shows that thermally processed MID-MIX ® treated sewage sludge produces an ash product that has potential to be beneficially used in cementitious materials for selected applications

Influence of combustion temperature on the performance of sewage sludge ash as a supplementary cementitious material

© 2018, Springer Japan KK, part of Springer Nature. The potential for using sewage sludge ash (SSA) as a supplementary cementitious material (SCM) has been investigated. Controlled combustion of sewage sludge collected in Croatia from two wastewater treatment plants produced SSA with different characteristics. These were used to substitute for cement in mortar samples. The chemical composition and physical properties of SSA depend on wastewater composition, the sludge treatment process and the combustion temperature. These factors influence the suitability of SSA to be used as a SCM. For three different combustion temperatures (800, 900 and 1000 °C), it was concluded that properties of fresh mortar were not affected while in the hardened state, the most favorable combustion temperature is 900 °C regarding mechanical properties. Regardless of combustion temperature, for all types of SSA used in mortars as cement replacement (up to 30%), the average decrease in both compressive and flexural strength values was less than 8% for every 10% of added SSA. The results presented indicate that using up to 20% replacement of cement by SSA produces mortars that meet the specific technical requirements analyzed in this work

USE OF SEWAGE SLUDGE ASH IN CEMENTITIOUS MATERIALS

The potential for using sewage sludge ash (SSA) in cement mortars and concrete is reviewed. The chemical and physical properties and pozzolanic activity of a range of different incinerated SSA samples indicates the potential to exploit the pozzolanic properties of this waste as a supplementary cementitious material (SCM). Using SSA as a SCM increases the water demand and reduces the workability, compressive strength and density of concrete mixes, although these adverse effects may be controllled by modifying the mix design. This represents a beneficial reuse application for a waste that is typically landfilled. However the use of SSA in cementitious materials must be carefully controlled because SSA varies significantly, depending on sludge production method and combustion conditions. Testing will therefore always be required to assess how a specific SSA behaves when incorporated in cementitious materials